+34 679 490 537info@nanbiosis.com

News U18

Non-Hodgkin lymphoma treatment with protein nanoparticles

A study result of collaboration between researchers of two NANBIOSIS units managed to produce a potent antitumor effect in an animal model with non-Hodgkin lymphoma

A non-Hodgkin’s lymphoma, NHL is a cancer that starts in white blood cells called lymphocytes, which are part of the body’s immune system.
Lymphoma. NHL is a term that’s used for many different types of lymphoma that share some characteristics.  The most prevalent type of non-Hodgkin lymphoma is called diffuse large B-cell lymphoma (LDCGB). Although there are treatments for this pathology, there are non-responders.

This nanoparticle can be developed as a nanopharmaceutical, in order to introduce a new treatment, which could be used in 40 percent of patients with non-Hodgkin lymphoma who do not respond to current therapy, and avoiding the adverse effects associated with conventional treatment.

The research conducted by the CIBER-BBN at the Hospital de Sant Pau, led by Ramón Mangues (Nanbiosis U18 Nanotoxicology Unit) and the Autonomous University of Barcelona, led by Antoni Villaverde Nanbiosis U1 Protein Production Platform (PPP) has demonstrated the high selectivity of a protein-based nanomedicine and created by the researchers themselves, for the targeted delivery of a toxin in the tumor cells to induce their selective death. The objective is that these nanoparticles can be developed as a nanopharmaceutical, which could be used in 40 percent of patients with non-Hodgkin lymphoma who do not respond to current therapy, avoiding the adverse effects associated with conventional treatment

This selective effect of the nanopharmaceutical is due to the specific interaction between a targeting peptide that contains the protein nanoparticle that carries the toxin and the CXCR4 cell receptor that is highly overexpressed in lymphoma cells. This is the first time that the uptake of protein nanoparticles in different organs of a hematological neoplasm is quantified.

This observation has shown that 86 percent of the administered dose accumulates in cancer cells, a substantial improvement compared to other non-protein nanoparticles or other drug targeting systems such as drug-antibody conjugates, which only reach 1 percent of the dose in the tumor.

As Ramón Mangues, Scientific Director of Nanbiosis U18 Nanotoxicology Unit, explains, “the new protein nanoparticle contains a ligand that identifies a CXCR4 receptor on the surface of cancer cells in which it enters selectively, reaching a very high uptake of the tumor and very low in the rest of the body, which greatly exceeds the tumor uptake of drugs used for this type of lymphoma.”

The bioluminescent follow-up of cancer cells and nanoparticle biodistribution and toxicity studies has been performed in the ICTS NANBIOSIS Nanotoxicology Unit Protein production has been partially performed by the ICTS “NANBIOSIS”, more specifically by the Unit of Protein Production Platform.

Read More

The first Nanocomposite that slows the spread of colon cancer

The creation of a nanodrug capable of blocking the spread of the disease, which is known as metastasis, has been highlighted by Guia Medica, as a heavy blow struck against to colon cancer, the malignant tumor with the highest incidence in our country, a process that affects 40% of the million cases of this type of cancer that are diagnosed every year in the world, and that represents the main cause of death.

The research, jointly carried out by scientists from the IIB Sant Pau, Sant Pau Hospital, the UAB, CSIC and CIBER-BBN, led by Esther Vázquez and Antonio Villaverde, Strategy Director of NANBIOSIS U1. Protein Production Platform (PPP) in the IBB-UAB and Ramon Mangues, Scientific Director of NANBIOSIS U18. Nanotoxicology Unit in the Sant Pau Hospital, were published in the scientific journal EMBO Molecular Medicine ando pen a new way to prevent metastasis in colorectal cancer in humans, using a nanomedicine that selectively eliminates metastatic stem cells.

NANBIOSIS Unit 18 of Nanotoxicology has been involved in the study of the biodistribution and the antimetastatic effect and on normal organs of the nanoconjugate administered and the unit and Unit 1 PPP, has contributed to the production of the protein part of the nanoconjugate.

The new drug works like a drone that identifies a receptor (CXCR4) in metastatic stem cells. Once localized, it administers the drug and destroys it, blocking the metastasis, according to research sources. By acting only on metastatic tumor cells, the new nanodrug avoids the general toxicity associated with the usual treatments against cancer and preserves healthy cells. Although up to now it has been successfully tested in animals suffering from colorectal cancer, the researchers who have carried out the trial believe that it could be used in 20 types of additional tumors, which also express CXCR4, as in prostate, breast, ovarian and other tumors.

Read More

NANBIOSIS Scientific Women in the International Day of Women and Girls in Science

Today February 11 is the International Day of Women and Girls in Science, a day to raise awareness of the gender gap in science and technology.

According to the United Nations, while yet women and girls continue to be excluded from participating fully in science, science and gender equality are vital to achieve the internationally agreed development goals, including the 2030 Agenda for Sustainable Development. Thus, in recent years, the international community has made a great effort to inspire and promote the participation of women and girls in science.

NANBIOSIS wants to acknowledge  the efforts made by scientific women who struggle every day to contribute their bit to Science and highlight their essential role in nowadays research. Especially we want to recognize the work of scientists women involved in our units, whatever is the nature of their contribution: technical, scientific development, management, coordination, direction, etc; just to mention some examples:
Neus Ferrer in the Scientific Direction of Unit 1 Protein Production Platform (PPP)
Pilar Marco and Nuria Pascual in the Management and Scientific Coordination of U2 Custom Antibody Service (CAbS) 
Miriam Royo in the Scientific Direction of U3 Synthesis of Peptides Unit
Laura Lechuga and M.Carmen Estevez in the Direction and Scientific Coordination of U4 Biodeposition and Biodetection Unit
Nora Ventosa and Nathaly Segovia in the Scientific Direction and Technical Coordination of U6 Biomaterial Processing and Nanostructuring Unit
Isabel Oliveira and Teresa Galán in the Coordination of U7 Nanotecnology Unit
Rosa Villa and Gemma Gabriel in the Management and Scientific Coordination of U8 Micro – Nano Technology Unit
Gema Martínez in the Scientific Coordination of U9 Synthesis of Nanoparticles Unit
Fany Peña in the Scientific Coordination of U13 Tissue & Scaffold Characterization Unit
Mª Luisa González Martín in the of Direction and Scientific Coordination of U16 Tissue & Scaffold Characterization Unit
Gemma Pascual and Isabel Trabado in the Coordination of the U17 Confocal Microscopy Service
Mª Virtudes Céspedes in the Scientific Coordination of U18 Nanotoxicology Unit
Beatriz Moreno in the Scientific Direction of Unit 19 Clinical tests lab
Ibane Abásolo in the Scientific Coordination of Unit 20 In Vivo Experimental Platformt
Verónica Crisóstomo in the Scientific Direction of Unit 24 Medical Imaging 

Ana Paula Candiota in the Scientific Coordination of Unit 25 Biomedical Applications I 
Maria Luisa García in the Scientific Direction of U28 NanoImaging Unit from Bionand, recently incorporated to NANBIOSIS

Read More

NANBIOSIS Against Cancer

The World Health Organization, the International Cancer Research Center (IARC) and the International Union Against Cancer (UICC) celebrate February 4 of each year as World Cancer Day

Every year, 14 million new cases of cancer are diagnosed worldwide and the disease causes 8.2 million deaths.

Thanks to scientific research, great advances have been made in the fight against cancer. Through surgery, chemotherapy or radio therapy and, in the last 20 years, through immunotherapy, hormonal treatment or cell therapies, tools have been obtained to improve early diagnosis and treatments, increasing cancer survival by 20%.

The only way to understand cancer and, someday, eradicate it or eliminate the suffering and death due to this disease, is RESEARCH

NANBIOSIS as an ICTS (Singular Scientific and Technical Infrastructures) for biomedical research plays a very important role in the fight against cancer. Some examples are bellow:

Thanks to a coordinated action between units U1 of Protein Production Platform (PPP), U18 of Nanotoxicology and U29 of Nucleic Acid Synthesis, NANBIOSIS is developing nanopharmaceuticals with a high degree of efficacy for the treatment of metastases in colon cancer, by using of proteins with high specificity of binding to metastatic cells and a high degree of permanence in the blood flow, loaded with anti-cancer drugs that are selectively released inside the tumor cells that are going to form the metastases. Through the public financing of a NEOTEC project and a RETOS-COLABORACION and the company NANOLIGENT SL, the first antimetastatic drug on the market will be developed.

The Protein Production Platform-PPP collaborates with research projects whose objective is the development of new cancer therapies based on recombinant modular proteins with the ability to self-assemble. These multimeric complexes have shown, in animal models, a high stability in serum and an improved biodistribution compared to that observed with drugs for clinical use. These principles have been valued in different types of cancer, including colorectal cancer and breast cancer. The modular design of these constructions allows the incorporation or substitution of direct peptides and therefore they are presented as a transversal tool for more effective treatments against cancer. In addition, the PPP has served the Vall d’Hebron Institute of Oncology (VHIO) of Barcelona, the Josep Vilanueva group (CIBERONC) in the field of biomarker study and new targets associated with triple negative breast cancer (TNBC).

Unit 6 of NANBIOSIS Biomaterial Processing and Nanostructuring Unit is working on a project in collaboration with VHIR, financed by the Spanish Goverment and CIBER-BBN, for the development of a new nanomedicine for the treatment of high-risk neuroblastoma, one of the most frequent childhood cancers.

Unit 6 is also working on the project Artificial Lymph Nodes for Cancer ImmunoTherapy (ALYCIA) A project born of a initiative of CIBER-BBN/ CIBERONC to enhance scientific interdisciplinary collaborations between research groups working on oncology and nanomedicine. Researchers of unit 6 will develop Artificial Lymph Nodes (ALN) based on dynamic 3D scaffolds able to promote efficient ex vivo lymphatic cell expansion of relevant phenotypes. Such ALN represent a new approach to lymphocyte expansion, which not only includes artificial Antigen Presenting Cells in suspension like the state-of-the-art expansion techniques, but also mimics the function of the LN ex vivo.

One of the singular capabilities of the U25 of NANBIOSIS NMR: Biomedical Applications I is the acquisition of high quality, high resolution preclinical magnetic resonance imaging/spectroscopy/spectroscopic imaging data. This allows performing leading-edge studies in preclinical cancer models such as noninvasive therapy response follow-up in murine brain tumours, revealing new response biomarkers with translational potential for brain cancer patients.

NANBIOSIS U4 Biodeposition and Biodetection Unit  is currently developing the national project PREDICT Point-of-care Nanoplasmonic Platforms for Novel High-Value Diagnostics and Therapy Follow-Up , which works in the early detection of lung cancer. PREDICT project will use the Unit 4 of Nanbiosis for the multiplexed biofunctionalization of the biosensor chips and their methodology optimisation.

Finally, Unit 20 of NANBIOSIS In Vivo Experimental Platform at VHIR, is the most implicated of the CIBER units on projects in the field of cancer, just to name some of them: H2020-NoCanTher: magnetic nanoparticles against pancreatic cancer through the use of hyperthermia combined with conventional treatment. H2020-Target-4-Cancer: nanotherapy based on polymeric micelles directed against specific receptors of tumor stem cells in colorectal cancer. H2020-DiamStar: nanodiamonds directed against leukemia for the potentiation of chemotherapy. FET-OPEN EvoNano: in silico and tumor-tumor models for the prediction of PK / PD and tumor efficacy of antitumor nanomedicines against tumor stem cells. FIS-ISCIII: polymeric micelles for siRNA and combined therapy against breast cancer tumor stem cells. CarboXigel: hydrogels for the sustained release of chemotherapeutic drugs against the metastatic spread of ovarian cancer. MelanoMir: nanomedicine applied to skin cancer, melanoma, beside other projects promoted by CIBER-BBN.

Read More

A new pathway for the prevention of metastasis in colorectal cancer in humans is open: a nanomedicine that selectively eliminates metastatic stem cells

Researchers of NANBIOSIS U18  Nanotoxicology Unit and U1. Protein Production Platform (PPP) at the Biomedical Research Institute of Sant Pau (IIB Sant Pau), of the Hospital of Santa Creu i Sant Pau, of the Universitat Autònoma de Barcelona (UAB), the Superior Council of Scientific Research (CSIC) and the Center for Biomedical Research in Network (CIBER) have published an article in one of the most prestigious international scientific journals in the field of Molecular Medicine, EMBO Molecular Medicine. This article demonstrates the efficacy of the  nanopharmaceutical  that selectively removes metastatic stem cells in animal models of colon cancer. The new drug works like a drone that has a ligand that identifies a receptor (CXCR4) in the metastatic stem cells, administers the drug and destroys these cells by blocking the metastasis.  The drug acts only on metastatic tumor cells and not on healthy cells, so it avoids the general toxicity associated with the usual treatments

This nanopharmaceutical has been successfully tested in animal models of colorectal cancer, but could be used in 20 additional tumor types that express CXCR4,
as in those of prostate, breast, ovary and others

This is the first drug in the world selectively antimetastatic that addresses the medical need to block metastatic spread, the main cause of death in cancer patients, while eliminating the toxicity and adverse effects of conventional treatments

The Hospital de Sant Pau could be the first center in the world to carry out clinical trials that evaluate this new drug in patients, prior to its possible introduction in clinical therapeutics

It has been observed that this receptor is overexpressed in at least 20 different types of cancer, including those of the prostate, breast, ovary and others not as common as the pancreas. This means that this nanoparticle can be targeted to treat different types of neoplasms, making it a very versatile vehicle that can transport different therapeutic molecules of high potency.

 

Article of reference:

María Virtudes CéspedesUgutz UnzuetaAnna AviñóAlberto GallardoPatricia ÁlamoRita SalaAlejandro Sánchez‐ChardiIsolda CasanovaMaría Antònia ManguesAntonio Lopez‐Pousa,Ramón EritjaAntonio VillaverdeEsther VázquezRamón Mangues.  Selective depletion of metastatic stem cells as therapy for human colorectal cancer. EMBO Molecular Medicine DOI 10.15252/emmm.201708772

The team of researchers, led by Dr. Ramón Magues de l’IIB Sant Pau, Prof. Antonio Villaverde of the UAB and Dr. Esther Vázquez of the UAB, have shown that the drug acts only on metastasis-initiating cells through its specific interaction between a peptide present in the protein nanoparticle that transports it and the cellular receptor CXCR4 that is overexpressed in tumor cells. This allows attacking only the tumor cells, blocking their dissemination in early stages, in a way that prevents the appearance of metastasis while avoiding the adverse effects derived from the usual treatments.

 

Nanoligent, a new spin-off to finance the nanoparticle

In June 2017, researchers from the IIB Sant Pau, from the Institute of Biotechnology and Biomedicine of the UAB and the CIBER from Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) who signed the article published now in EMBO Molecular Medicine created a spin-off, Nanoligent , with the aspiration to develop the first drug designed to eliminate metastatic cells.

This company, which has more than 10 years of studies behind it, is directed by Dr. Manuel Rodríguez Mariscal, a professional with a long experience in the field of investment and the creation of biotechnology companies and aims to obtain financing for the realization of the project.

Read More

Nanoparticle uptake and in vivo estimates of therapeutic efect and toxicity

Ramón Mangues, Scientific Dierctor of unit 18 of NANBIOSIS, Unit of nanotoxicology, explains in this video some of the animal models used in the unit for preclinical validation of nanoparticles, especially of application in cancer

Read More

The general consul of France meets with NANBIOSIS researchers

The general consul of France in Barcelona, ​​Mr. Cyril Piquemal visited the IBB UAB facilities last July 18, to find out about the research that is being carried out and, in particular, explore possible collaborations in nano-pharmacy development projects.

During the visit, the Consul of France in Barcelona was received by Màrius Martínez, Vice President of International Relations at the UAB; Maite Paramio, Deputy Vice President; Ivan Martínez, vice president of Research; Salvador Ventura, director of the Institute of Biotechnology and Biomedicine, and Antonio Villaverde, head of the IBB Nanotechnology Unit-NANBIOSIS  U1. Protein Production Platform (PPP)

Next, the mayor visited the facilities and laboratories of the Institute and met with the researchers Esther Vázquez and Antonio Villaverde, (NANBIOSIS  U1. Protein Production Platform (PPP)), and Ugutz Unzueta and Ramón Mangues, (NANBIOSIS Unit 18  Nanotoxicology Unit)  at the Institute of Research of the ‘Hospital de la Santa Cruz and San Pablo, to find out about the research in the development of nanoparticles for metastases treatment by means of the selective elimination of tumor stem cells.

In addition, the researchers explained to the consul the case of the spin-off Nanoligent, to show a project born from the research  and whose objective is to develop the first selective drug to treat metastasis

The purpose of the meeting was to explore possible collaborations between the University and the Consulate, an entity that aims to connect research groups and venture capital funds with the Catalan biotechnology ecosystem.

Read More

Nanomedicine to fight against the spread of cancer

Nanoligent, S.L., the company stablished on March 2017 by professors Dr. A. Villaverde and Dra. E. Vázquez from NANBIOSIS Unit 1, professor Dr. M. Mangués from NANBIOSIS Unit 18, and entrepreneur Dr. M. Rodríguez is highlighted in la Vanguardia.

More information here

 

Read More

Selective CXCR4+ Cancer Cell Targeting and Potent Antineoplastic Effect by a Nanostructured Version of Recombinant Ricin

Researchers of NANBIOSIS Unit 1 and NANBIOSIS Unit 18, led by Prof Antoni Villaverde have published the article “Selective CXCR4+ Cancer Cell Targeting and Potent Antineoplastic Effect by a Nanostructured Version of Recombinant Ricin” at SMALL journal.

Under the unmet need of efficient tumor‐targeting drugs for oncology, a recombinant version of the plant toxin ricin (the modular protein T22‐mRTA‐H6) is engineered to self‐assemble as protein‐only, CXCR4‐targeted nanoparticles. The soluble version of the construct self‐organizes as regular 11 nm planar entities that are highly cytotoxic in cultured CXCR4+ cancer cells upon short time exposure, with a determined IC50 in the nanomolar order of magnitude. The chemical inhibition of CXCR4 binding sites in exposed cells results in a dramatic reduction of the cytotoxic potency, proving the receptor‐dependent mechanism of cytotoxicity. The insoluble version of T22‐mRTA‐H6 is, contrarily, moderately active, indicating that free, nanostructured protein is the optimal drug form. In animal models of acute myeloid leukemia, T22‐mRTA‐H6 nanoparticles show an impressive and highly selective therapeutic effect, dramatically reducing the leukemia cells affectation of clinically relevant organs. Functionalized T22‐mRTA‐H6 nanoparticles are then promising prototypes of chemically homogeneous, highly potent antitumor nanostructured toxins for precise oncotherapies based on self‐mediated intracellular drug delivery.

See article: https://doi.org/10.1002/smll.201800665

Read More

Self-assembling toxin-based nanoparticles as self-delivered antitumoral drugs

Scientists of NANBIOSIS  Units U1. Protein Production Platform (PPP),  and U18. Nanotoxicology Unit, have recently published an article titlled “Self-assembling toxin-based nanoparticles as self-delivered antitumoral drugs” in the Journal of  Controlled Release.

Loading capacity and drug leakage from vehicles during circulation in blood is a major concern when developing nanoparticle-based cell-targeted cytotoxics. To circumvent this potential issue it would be convenient the engineering of drugs as self-delivered nanoscale entities, devoid of any heterologous carriers. In this context, we have here engineered potent protein toxins, namely segments of the diphtheria toxin and the Pseudomonas aeruginosa exotoxin as self-assembling, self-delivered therapeutic materials targeted to CXCR4+ cancer stem cells. The systemic administration of both nanostructured drugs in a colorectal cancer xenograft mouse model promotes efficient and specific local destruction of target tumor tissues and a significant reduction of the tumor volume. This observation strongly supports the concept of intrinsically functional protein nanoparticles, which having a dual role as drug and carrier, are designed to be administered without the assistance of heterologous vehicles.

Read More